Ovarian cancer forms in tissues of an ovary (one of a pair of female reproductive glands in which the ova, or eggs, are formed). Most ovarian cancers are either ovarian epithelial carcinomas (cancer that begins in the cells on the surface of the ovary) or malignant germ cell tumors (cancer that begins in egg cells). According to the National Cancer Institute, ovarian cancer is the seventh most common cancer, with an estimated 20,180 new cases in 2006, but is the fourth most deadly, with an estimated 15,310 deaths in 2006.
A possible genetic contribution to ovarian cancer risk is indicated by the increased incidence of this cancer among women with a family history, and by the observation of rare families in which multiple family members are affected with ovarian cancer, in a pattern compatible with autosomal dominant inheritance of cancer susceptibility. Formal studies of families (linkage analysis) have subsequently proven the existence of autosomal dominant predispositions to ovarian cancer and have led to the identification of several highly penetrant genes as the cause of inherited cancer risk in many cancer-prone families. Mutations in these genes are rare in the general population and are estimated to account for no more than 5% to 10% of ovarian cancer cases overall.
Although reproductive, demographic, and lifestyle factors affect risk of ovarian cancer, the single greatest ovarian cancer risk factor is a family history of the disease. A large meta-analysis of 15 published studies estimated an odds ratio (OR) of 3.1 for the risk of ovarian cancer associated with at least one first-degree relative with ovarian cancer.
Despite recent improvements, initial or first-line chemotherapy fails to produce a remission in more than 70% of patients with ovarian cancer. Furthermore, approximately 40-50% of the women who do achieve a remission after first-line chemotherapy will experience a recurrence of cancer within 3 years. Patients with recurrent ovarian, peritoneal, or fallopian tube cancer generally have a poor outcome with current therapies. There is a need for effective treatment method for patients with recurrent ovarian cancers. Preferably, the treatments overcome the shortcomings of current drug and transplant treatments, such as hypersensitivity reactions due to the solvent/surfactant in which drugs are dissolved.
Many anti-proliferative agents are dissolved in a solvent/surfactant which produces hypersensitivity reactions. Great efforts have been invested on the development of water soluble prodrugs and derivatives of anti-proliferative agents with higher hydrophilic groups to enhance water solubility and thus obviate the need for potentially toxic solvents/surfactants. Another approach to address the problem associated with the poor water solubility of anti-proliferative agents is the development of various formulations such as nanoparticles, oil-in-water emulsions, and liposomes. For example, Abraxane® is a nanoparticle composition of paclitaxel and albumin. Nanoparticle compositions of substantially poorly water soluble drugs and uses thereof have been disclosed, for example, in U.S. Pat. Nos. 5,916,596; 6,096,331; 6,749,868; and 6,537,579; U.S. Patent Appln. Pub. No. US20030199425; and PCT Application Pub. Nos. WO98/14174, WO99/00113, WO07/027,941 and WO07/027,819. Administration of Abraxane® to a patient with recurrent ovarian cancer is described in Mida et al., Gynecologic Oncology, 100:437-438 (2006).
The disclosures of all publications, patents, patent applications and published patent applications referred to herein are hereby incorporated herein by reference in their entirety.